Mosaic analysis of insulin receptor function.
Mosaic analysis of insulin receptor function.
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胰岛素受体功能的镶嵌分析。
DOI：
10.1172/jci17810
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Accili,Domenico
中科院分区：
文献类型：
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作者：
Kitamura,Tadahiro;Kitamura,Yukari;Nakae,Jun;Giordano,Antonio;Cinti,Saverio;Kahn,CRonald;Efstratiadis,Argiris;Accili,Domenico
胰岛素促进新陈代谢和生长。然而，目前尚不清楚胰岛素依赖性生长是否仅仅是其代谢作用的结果。靶向消融胰岛素受体（Insr）还没有澄清这个问题，因为早期产后死亡。为了研究这个问题，我们产生了具有可变细胞嵌合的小鼠，这些小鼠具有零linsralles。在大约80%的细胞中植入会导致极端的生长迟缓、脂肪萎缩和低血糖，这是一种类似于人类小妖精综合症的临床症状。在98%的细胞中植入，虽然导致类似的生长迟缓和脂肪萎缩，但没有β细胞增生引起糖尿病。生长迟缓与肝胰岛素样生长因子结合蛋白-1的表达增加60倍以上相关。这些发现表明，胰岛素独立于代谢调节生长，胰岛素受体的数量是胰岛素作用特异性的重要决定因素。
Insulin promotes both metabolism and growth. However, it is unclear whether insulin-dependent growth is merely a result of its metabolic actions. Targeted ablation ofinsulin receptor(Insr) has not clarified this issue, because of early postnatal lethality. To examine this question, we generated mice with variable cellular mosaicism for nullInsralleles.Insrablation in approximately 80% of cells caused extreme growth retardation, lipoatrophy, and hypoglycemia, a clinical constellation that resembles the human syndrome of leprechaunism.Insrablation in 98% of cells, while resulting in similar growth retardation and lipoatrophy, caused diabetes without β-cell hyperplasia. The growth retardation was associated with a greater than 60-fold increase in the expression of hepaticinsulin-like growth factor binding protein-1. These findings indicate that insulin regulates growth independently of metabolism and that the number of insulin receptors is an important determinant of the specificity of insulin action.